The coronavirus can develop resistance to the drug remdesivir, as anticipated by laboratory studies and now verified in humans for the first time.

Experts use vaccines as well as formulations containing the active ingredient remdesivir in the battle against Covid-19.

The substance prevents the virus multiplying by blocking the viral ‘copying machine’ known as RNA polymerase. RNA polymerases are enzymes (proteins) that can read the genetic code and translate it into RNA (ribonucleic acid). 

Among others, former US President Donald Trump was treated with it after being infected with the coronavirus.

Although remdesivir was classified as ineffective in COVID treatment in a study by the World Health Organization (WHO), it continued to be used worldwide – including in a 70-year-old Covid 19 patient in the USA, whose case is presented in the journal “Nature Communications”. This shows that the coronavirus can develop resistance to the active ingredient.

Remdesivir failed

The immunocompromised woman had been treated with the antibody rituximab for non-Hodgkin lymphoma. After that, according to the team at Yale University School of Medicine in New Haven, Connecticut, she was no longer able to develop antibodies against Covid-19 infection. After 148 days, she was treated with remdesivir. For ten days instead of the usual five. There was no success.

The viral load fell, as the rising ct value showed. However, a relapse occurred during the treatment: the ct value dropped significantly. Only the combined administration of the antibodies casirivimab and imdevimab, which were still effective against the variant that was circulating at the time, was able to end the infection.

Unlikely to spread

The reason for the weakening of remdesivir is a mutation of the virus: E802. It was first detected in the patient on day 7 of remdesivir treatment. After a few days, it had prevailed over other variants. E802 changes the RNA polymerase in such a way that it can only be slightly inhibited by remdesivir. 

Researchers had already described the possibility in 2021 after laboratory studies in the journal “Plos Pathogens”.

The mutation not only ensures that remdesivir becomes ineffective. It also reduces the infectivity of Sars-CoV-2. Accordingly, the virus would not be able to assert itself under normal circumstances. Only if remdesivir prevents the replication of other variants, as in the case of the 70-year-old, do mutations with E802 have a chance. So it cannot be assumed that they will spread.

What does ct value mean?

Ct stands for “cycle threshold”. The value designated in this way indicates how many cycles of heating and cooling a sample a PCR sample must go through before a relevant amount of virus genetic material can be detected. If the value is low – that is, the genetic material can be detected after a short time – the viral load is high and the patient is more infectious than if the sample shows a high ct value. With Sars-CoV-2, a ct value of more than 30 means that the infectivity is usually low to negligible.

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